The purpose of the proposed research is to reveal principles of nervous system function in the control of basic behavior patterns such as feeding and mating. We are finding that hypothalamic reward and punishment mechanisms serve a regulatory function by translating physiological imbalances into corrective behavioral action. Electrical stimulation of certain brain regions can be rewarding as evidenced by self-stimulation behavior, or it can cause aversion shown by responses to escape from stimulation. Our research is demonstrating that lateral hypothalamic self-stimulation and stimulation-escape are controlled by the same oral, postingestional and weight related factors which control feeding. The factors which augment food intake increase the reward of self-stimulation and decrease escape; conversely, satiety factors cause a shift from reward to aversion. It therefore appears that hypothalamic reward is involved in rewarding eating when the animal is hungry, and hypothalamic aversion is involved in punishing eating when the animal is satiated. Similarly for mating, we find hypothalamic sites where self-stimulation decreases after castration, with reversal by androgen therapy; whereas stimulation-escape increases after ejaculation. Apparently this is a reward-aversion system controlling mating. For the next five years we plan two major projects. The first is aimed at separating the neural substrates for stimulation-induced reward, aversion, feeding and arousal. The primary technique will be selective depletion of monoamine neurotransmitters, norepinephrine and serotonin which we find play a role in satiety and drug-induced anorexia. The second project is a study of the sensory control of brain stimulation reward and aversion. The focus is on (a) glucostatic control of lateral hypothalamic reinforcement and mating. In summary, we propose: to analyze the neurochemical control of brain stimulation reinforcement and examine its relation to the physiological mechanisms which control natural behavior.